Impairments in new learning and memory are among the most common deficits in persons with Multiple Sclerosis (MS). Our NIH funded clinical trial (RO1 HD045798) is a randomized, double blind, placebo- controlled clinical trial designed to remediate learning and memory in persons with MS using specific behavioral techniques which target the primary deficit: impairments in the acquisition (or learning) of new information. Individuals with MS, are randomly assigned to a memory retraining group or a placebo control group. Outcome is measured through: (1) a traditional neuropsychological (NP) battery and (2) an assessment of global functioning (AGF) examining the impact of the treatment on daily activities. While this funded study will be able to demonstrate behaviorally any potential benefits of the targeted intervention for impaired learning and memory, it does not provide information on what changes are occurring in the brain following treatment. The currently proposed grant supplement will examine the impact of the targeted behavioral intervention on functional cerebral activity using functional Magnetic Resonance Imaging (fMRI). We aim to demonstrate that changes at the level of the cerebral substrate also accompany the behavioral changes in learning and memory noted following treatment. We will determine if improvement in learning and memory is associated with particular patterns of functional, cerebral activity on fMRI. To meet these objectives, we seek to supplement our currently funded clinical trial. Subjects will receive pre and post- treatment fMRI evaluations, which will be correlated with behavioral performance assessed concurrently. Additionally, participants will complete a 6-month post-treatment fMRI to examine the maintenance of treatment effects over time, as well as the impact of "booster sessions" to facilitate the maintenance of treatment effects from a neurofunctional perspective. The NIH recommends research analyzing existing rehabilitation techniques, empirically assessing their validity, and providing justification to the consumer and practitioner for the advancement of the field of medical rehabilitation research and recognizes this as a high priority research area. Our study is designed to specifically address these issues. [unreadable] [unreadable] [unreadable]